This proposal requests funds for the purchase of a new electrospray tandem quadrupole orthogonal-acceleration time-of flight mass spectrometer (Q- TOF). This shared instrument will be used for structural studies of bio- macromolecules and their myriad covalent modifications that are of critical importance to on-going research in the biological and medical sciences in the San Francisco Bay Area. It will be housed in the NIH NCRR- supported Mass Spectrometry Resources at UCSF. This environment ensures the availability of the scientific, technical and management expertise required to optimize its productive in solving problems at the forefront of macromolecular biology and medicine for a large number of investigators. The proposed instrumentation will provide previously unavailable absolute sensitively for on-line capillary separation-ES1 MS/MS to project investigators with electrospray experience and established needs. The major users are a group of 20 scientists and clinicians involved in over 50 NIH-supported research programs. These research projects are at the forefront of biomedical problems concerning the identification of native and covalently modified peptides, proteins, carbohydrates and nucleic acids required in deciphering cell function and dysfunction. Most of these studies require the high absolute sensitivity and performance of the instrument requested. Prof. George L. Kenyon, Dean of the School of Pharmacy, will chair the Advisory Committee responsible for the overall guidance of the shared instrument's use. The committee will assure that the time is shared equitably and that some 10% of its time will be made available to other projects requiring its unique capability. The School will contribute $160,820.00 toward this purchase. Mr. David Maltby, who has extensive experience in electrospray and other types of biological mass spectrometry, will oversee scheduling, training and maintenance and will provide daily supervision of usage. Long term productive usage and maintenance will be assured by the close association with a major Mass Spectrometry Facility and financial support of the major users.